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Results for “Extracellular Matrix”

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PubMed2002

[Changes in extracellular matrix of endothelial cells co-cultured with VSMC under shear stress].

The construction and amount of fibronectin (Fn), laminin (Ln) and collagen type IV (ColIV) in the extracellular matrix of endothelial cells (EC) co-cultured with vascular smooth muscle cells (VSMC) under shear stress were studied by immuno-fluoro-cytochemistry, laser confocal scanning microscopy and image analysis methods to detect the effect of shear stress on adhesion of EC for vascular tissue engineering. One group of EC was maintained under static conditions as a control. In the control, both Fn and Ln exhibited as a granular pattern in perinuclear area and a fibrillar pattern localized underneath EC, and Col IV exhibited mainly as the granular in the perinuclear area, but the fibrillar was fewer. On exposure of EC to shear stress in physiological range, Fn grouped into fibril tracts, and there was a tendency for some of these tracts of fibrils to align with direction of shear stress. Ln and Col IV also grouped into fibril tracts, which, in contrast to Fn, were randomly oriented, Simultaneously, all contents of the extracellular matrix had different quantitative alterations. These results suggest that the capability of adhesion of EC co-cultured with VSMC may be strengthened under shear stress.

Animals↗

PubMed1995

Immunohistochemical quantitation for extracellular matrix proteins in rats with glomerulonephritis induced by monoclonal anti-Thy-1.1 antibody.

Extracellular matrix proteins (type I collagen and fibronectin) in frozen histologic sections of kidney cortex from rats with glomerulonephritis induced by a single intravenous administration of anti-Thy 1.1 antibody were quantified using an immunohistochemical micromethod. Type I collagen and fibronectin contents in renal cortex of rats with experimental glomerulonephritis (4.33 +/- 0.79 and 10.41 +/- 2.01 microgram/mg of total protein, respectively) were 262% and 151%, respectively, higher than in control rats given normal mouse IgG (1.65 +/- 0.16 and 6.88 +/- 0.95 microgram/mg, respectively; p < 0.01 in each case). In the glomerulonephritic rats, the increase in the contents of extracellular matrix proteins, especially type I collagen, correlated with increasing glomeruli with expansion of mesangial areas. The increase in type I collagen content correlated well with increasing urinary protein excretion and blood urea nitrogen and serum total cholesterol levels (r = 0.851, 0.812, and 0.837, respectively; p < 0.05 in each case). The decrease in creatinine clearance correlated with increasing content of type I collagen (r = 0.781; p < 0.05). The immunohistochemical micromethod may make it possible to evaluate the histopathological diagnosis of mesangial proliferative glomerulonephritis quantitatively.

Animals↗

PubMed1985

Extracellular matrix in hepatic granulomas of mice infected with Schistosoma mansoni. Qualitative and quantitative analysis.

To investigate the role of extracellular matrix molecules in the granulomatous inflammation, cercariae of Schistosoma mansoni were injected subcutaneously into BALB/c mice. Well-organized granulomas consisting mainly of stimulated macrophages and epithelioid cells developed in the liver at 11 weeks after infection, thereafter showing a tendency to heal. Fibronectin and heparan sulfate proteoglycan deposition appeared around parasite eggs, then increased distinctly at 11 weeks after infection, and subsequently diminished. Quantities of glycosaminoglycans and hydroxyproline in the egg lesion increased significantly at 11 weeks after infection. Thereafter, the amounts of glycosaminoglycans decreased, whereas hydroxyproline content did not. The data suggest that fibronectin and other macromolecules interact to form granuloma extracellular matrix, and that these extracellular events participate in the development of granulomatous inflammation and subsequent fibrosis induced by schistosome eggs.

Animals↗

PubMed1994

Proteins of the inter-alpha-trypsin inhibitor family stabilize the cumulus extracellular matrix through their direct binding with hyaluronic acid.

We have previously identified a glycoprotein of the inter-alpha-trypsin inhibitor family of proteins as a serum factor responsible for the stabilization of the expanding cumulus mass. In this study, the mechanism of interaction of this cumulus extracellular matrix stabilizing factor (cESF) with hyaluronic acid (HA) has been explored. It was found that the pH optimum for binding of cESF and HA is 7 and that binding is sensitive to ionic strength. The dissociation constant is about 1.9 x 10(-8) M in 10 mM sodium phosphate buffer (pH 7.2). Circular dichroism studies show that cESF contains about 24% alpha-helical and 42% beta-sheet structure. Gross conformational changes in cESF, however, are not detected in the presence of HA. We also found that modification of lysine residues of cESF with citraconic anhydride greatly reduced its binding with HA and completely abolished its cumulus stabilizing activity, and deblocking lysine residues restored its capacity to bind with HA and its cumulus matrix stabilizing activity. This evidence supports the hypotheses that cESF stabilizes the expanding cumulus extracellular matrix by directly binding with HA and that cESF may serve as a structural protein to organize the formation of the cumulus extracellular matrix. Our evidence also supports the view that binding of cESF and HA is through a stereo-specific charge interaction. Putative binding sites of cESF that interact with HA are postulated.

Alpha-Globulins↗

PubMed2004

Expression of extracellular matrix components versican, chondroitin sulfate, tenascin, and hyaluronan, and their association with disease outcome in node-negative breast cancer.

PURPOSE: The purpose is to determine whether the levels of expression of extracellular matrix components in peritumoral stroma are predictive of disease outcome for women with node-negative breast cancer. EXPERIMENTAL DESIGN: Tumor tissue from 86 patients with node-negative breast cancer was examined by immunohistochemical staining for the expression of versican, chondroitin sulfate (CS), tenascin, and hyaluronan (HA). With the exception of HA, the expression of the extracellular matrix components was measured by video image analysis. Statistical correlation of the immunohistochemical data with clinicopathological characteristics and disease outcome was performed. RESULTS: All of the extracellular matrix components were present in the peritumoral stroma of the entire study cohort. In contrast, immunoreactivity within the cancer cell was observed in 82% of tumors for HA, 12% for CS, and 4% for tenascin; no immunostaining of cancer cells for versican was observed for any of the tumors. Cox regression and Kaplan-Meier analyses indicated that elevated expression of stromal versican predicted increased risk and rate of relapse in this cohort. Elevated expression of tenascin was predictive of increased risk and rate of death only. Although neither CS nor HA were predictive of disease outcome in this cohort, tumor size was predictive of increased risk and rate of both relapse and survival. CONCLUSIONS: Elevated expression within peritumoral stromal matrix of versican and tenascin was predictive of relapse-free and overall survival, respectively, in women with node-negative breast cancer.

Adult↗

PubMed2004

Expression of extracellular matrix metalloproteinase inducer in human placenta and fetal membranes at term labor.

Matrix metalloproteinases (MMPs) are the main mediators of extracellular matrix (ECM) degradation during human parturition. However, the mechanisms involved in regulation of MMP production during parturition remain poorly understood. Recently, an extracellular matrix metalloproteinase inducer (EMMPRIN) has been shown to play a key role, as a local regulator, in stimulating MMP production in cancer systems. Whether EMMPRIN is expressed and stimulates MMP production in human placenta and fetal membranes is presently unknown. In this study, we investigated the expression of EMMPRIN at the levels of mRNA and protein in human term placenta and fetal membranes with or without labor. Western blot analysis showed that EMMPRIN protein was detected in term placenta and fetal membranes at two molecular masses of 40 and 65 kDa (glycosylated protein) and one of approximately 30 kDa (nonglycosylated protein). The ratio of 65 kDa EMMPRIN to total EMMPRIN significantly increased (P < 0.05) in term labor chorio-decidua and amnion compared with nonlabor chorio-decidua and amnion. Immunohistochemical analysis revealed that EMMPRIN was expressed in placental syncytiotrophoblast, amniotic epithelial cells, trophoblast cells of chorion laeve, and decidua parietalis. EMMPRIN was also detected at the mRNA level using RT-PCR in cultured placental syncytiotrophoblast, amniotic epithelial cells, and chorionic trophoblast cells. We conclude that human placenta and fetal membranes express EMMPRIN, with the potential to stimulate MMP production, thereby facilitating fetal membrane rupture and leading to detachment of the placenta and fetal membranes from the maternal uterus at the time of parturition.

Amnion↗

PubMed1999

Effect of cell plating density and extracellular matrix protein on cell growth of epithelial rests of Malassez in vitro.

The present study investigated how cell plating density and extracellular matrix protein influence cell survival of epithelial rests of Malassez (ERM) in vitro. ERM cells were plated on culture dishes coated with laminin (LM), type IV collagen (type IV), or fibronectin (FN), or on noncoated dishes, (Non) at a cell density of 2 x 104-1 x 105/ml in a nonserum culture medium. XTT assays were performed to calculate the number of cells attached on the substrata after 6, 24, 48, and 72 h. Mean cell numbers were calculated, and significant differences were determined using ANOVA. When epithelial cells were cultured on various matrices at a cell density of less than 2 x 104/ml, the cells did not grow and then fell into apoptotic cell death, which was confirmed by transmission electron microscopy. The cell number was significantly increased in cells plated on FN compared to those on Non at a cell density of 4 x 104/ml-8 x 104/ml. These results suggest that both extracellular matrix proteins and cell-cell interactions may contribute to prevent apoptosis of ERM in vitro. Cell-cell interactions may be a more important factor than exogenous extracellular matrix proteins for the survival of ERM cells in vitro.

Journal Article↗

PubMed1993

Effect of retinyl acetate on the assembly of the fibronectin extracellular matrix and the processing of the fibronectin receptor beta subunit of confluent C3H/10T1/2 mouse embryo fibroblasts.

The mouse embryo fibroblast cell line, C3H/10T1/2, synthesized and deposited a large amount of fibronectin especially in the pericellular matrix. Confluent cultures of these cells cultured in the presence of 0.3 micrograms/ml of retinyl acetate released cell surface fibronectin and the extracellular matrix fibronectin fibrils were disorganized. The immunoblot analysis demonstrated that the number of the fibronectin receptor was decreased in the prolonged culturing of retinyl acetate-treated cells. Immunoprecipitation of 35S-methionine pulse-chase labeled cell extracts by antifibronectin receptor antibody indicated that about one-half of the pre-beta subunit was processed and converted to the mature form in control cells, and only about one-fourth of the pre-beta subunit was processed in the retinyl acetate-treated confluent cells. 1-deoxymannojirimycin (MNJ), which is an inhibitor of oligosaccharide processing, induced disorganization of the extracellular matrix fibronectin assembly similar to that observed with retinyl acetate. The results of this study suggest that a mechanism of action of retinyl acetate is inhibition of the glycosylation during processing of the fibronectin receptor, a step necessary for fibronectin binding and for assembly of the extracellular matrix.

Animals↗

PubMed1999

Regulation of tumor cell invasion by extracellular matrix.

The ability of malignant tumor cells to invade normal surrounding tissue contributes in large part to the significant morbidity and mortality of these cancers. The process of invasion involves adherence of the tumor cells to the extracellular matrix (ECM), degradation of matrix components, and movement of the cell body. Attachment-to ECM molecules is mediated by the integrin family of extracellular matrix receptors. Integrins are a large family of heterodimeric proteins which transduce a variety of signals from the ECM. Ligand occupancy is critical for activation of integrin signaling. This signaling may occur via several different pathways. One of the best characterized of these pathways is the mitogen activated protein kinase (MAPK) cascade. This serial phosphorylation of substrate proteins terminates in activation of transcription factors which regulate expression of target genes. Many of these genes are critical for extracellular matrix degradation or cell migration. Among these are the matrix metalloproteinases (MMPs), a large family of ECM-degrading enzymes. Regulatory elements in the promoters of MMPs have been characterized, providing insight into how MMP expression is controlled. This review focuses on mechanisms by which the ECM regulates tumor cell invasion through integrin signaling via the MAPK pathway using MMP expression as the model.

Animals↗

PubMed2004

Latent TGF-beta binding proteins: extracellular matrix association and roles in TGF-beta activation.

Transforming growth factor betas (TGF-betas) are multifunctional and pleiotropic growth factors. Their major effects include inhibition of cell proliferation and enhancement of extracellular matrix production. TGF-betas are secreted from cells as latent complexes, consisting of mature dimeric growth factor, the latency-associated propeptide (LAP), and a distinct gene product, latent TGF-beta binding protein LTBP. The secreted complex is targeted to specific locations in the extracellular matrix by the appropriate LTBP. The latent complex needs subsequently to be activated. Most studies describing biological effects of TGF-beta have been carried out in cell cultures using high concentrations of active, soluble TGF-beta, where appropriate targeting of the growth factor is missing. However, TGF-beta is produced and secreted in vivo as a latent complex in a specific and targeted manner. Various experimental approaches have convincingly shown the importance of the activation of latent TGF-beta, as well as the importance of LTBPs as targeting molecules of the effects of TGF-beta. Essential steps in the activation appear to be cellular recognition of extracellular matrix-associated LTBPs and subsequent recognition of the associated latent TGF-beta. Cell recognition by specific molecules like integrins and proteolytic events involving plasminogen activation evidently play multifaceted roles in the regulation of TGF-beta activation.

Adaptation, Physiological↗

PubMed1992

Thrombospondin as a component of the extracellular matrix of epiretinal membranes: comparisons with cellular fibronectin.

We compared the distribution of the adhesive extracellular matrix glycoproteins thrombospondin and cellular fibronectin in epiretinal membranes. A total of nine membranes were investigated with immunohistochemical techniques. Thrombospondin and cellular fibronectin immunoreactivity were observed in seven of the specimens and immunostaining for the two glycoproteins was co-localised in four of the membranes. The findings indicate that thrombospondin contributes to the extracellular glycoprotein content of epiretinal membranes and is frequently co-distributed with cellular fibronectin in the tissue. As a consequence, thrombospondin may play a role in the assembly of the extracellular matrix of epiretinal membranes.

Diabetic Retinopathy↗

PubMed2001

[Investigation on the mechanics of adhesion to the selective extracellular matrix coated surfaces of lung cancer cells].

The adhesion properties of tumor cells with extracellular matrix(ECM) are closely associated with their invasion and metastasis. Our work reported here was intended reveal the relevant biomechanical and biorheological manifestations of human lung cancer. Using micropipette aspiration technique, we investigated quantitatively the adhesive mechanics properties of high metastatic human giant cell carcinoma(PG) cells as well as low metastatic adenocarcinoma(PAa) cells of lung based on cell culture in vitro. The results showed that the adhesion forces of PAa and PG cells to collagen IV were significantly higher than those to glass surfaces, but at the lower concentrations(1.00 microgram/ml and 2.00 micrograms/ml) of collagen IV, the amplitude for the increase of adhesion forces of PG cells were less than the amplitude for that of PAa cells, and most of the adhesion force values of PAa cells to the coated surfaces of incorporation of laminin along with 2 micrograms/ml collagen IV were significantly greater than those of PG cells. At the lower concentrations(0.625 microgram/ml for PAa cells, and 0.625 microgram/ml, 1.25 micrograms/ml for PG cells) of laminin tested, the adhesion force values of PAa and PG cells all decreased, but the amplitude and level for the decreased values of adhesion forces of PG cells were greater than those for the PAa cells. In conclusion, the adhesive and proteolytic behaviour of cancer cells to extracellular matrix might be mediated mainly by tumor cell membrane receptors such as integrin receptors and laminin receptors, it might affect the biological characteristics and the metastasis of the tumor cells. The results may benefit to explain some questions in biomechanical views about how the highly metastatic PG cells are prone to migration and invasion.

Adenocarcinoma↗

PubMed2007

Degradation of extracellular matrix and its components by hypobromous acid.

EPO (eosinophil peroxidase) and MPO (myeloperoxidase) are highly basic haem enzymes that can catalyse the production of HOBr (hypobromous acid). They are released extracellularly by activated leucocytes and their binding to the polyanionic glycosa-minoglycan components of extracellular matrix (proteoglycans and hyaluronan) may localize the production of HOBr to these materials. It is shown in the present paper that the reaction of HOBr with glycosaminoglycans (heparan sulfate, heparin, chondroitin sulfate and hyaluronan) generates polymer-derived N-bromo derivatives (bromamines, dibromamines, N-bromosulfon-amides and bromamides). Decomposition of these species, which can occur spontaneously and/or via one-electron reduction by low-valent transition metal ions (Cu+ and Fe2+), results in polymer fragmentation and modification. One-electron reduction of the N-bromo derivatives generates radicals that have been detected by EPR spin trapping. The species detected are consistent with metal ion-dependent polymer fragmentation and modification being initiated by the formation of nitrogen-centred (aminyl, N-bromoaminyl, sulfonamidyl and amidyl) radicals. Previous studies have shown that the reaction of HOBr with proteins generates N-bromo derivatives and results in fragmentation of the polypeptide backbone. The reaction of HOBr with extracellular matrix synthesized by smooth muscle cells in vitro induces the release of carbohydrate and protein components in a time-dependent manner, which is consistent with fragmentation of these materials via the formation of N-bromo derivatives. The degradation of extracellular matrix glycosaminoglycans and proteins by HOBr may contribute to tissue damage associated with inflammatory diseases such as asthma.

Animals↗

PubMed1992

In vivo interactions of TGF-beta and extracellular matrix.

TGF-beta, a multifunctional cytokine, plays an important role in embryogenesis and in regulating repair and remodeling following tissue injury. Many of the biological actions of TGF-beta are mediated by widespread effects on deposition of extracellular matrix. TGF-beta stimulates the synthesis of individual matrix components including proteoglycans, collagens and glycoproteins. TGF-beta also blocks matrix degradation by decreasing the synthesis of proteases and increasing the synthesis of protease inhibitors. Finally, TGF-beta increases the synthesis of matrix receptors and alters their relative proportions on the surface of cells in a manner that could facilitate adhesion to matrix. All of these events have largely been demonstrated in vitro in cultured cells. In an experimental model of glomerulonephritis we have shown that TGF-beta is responsible for the accumulation of pathological matrix in the glomeruli following immunological injury. Furthermore, all three of TGF-beta's actions on extracellular matrix--increased synthesis, decreased degradation and modulation of receptors--have now been documented to be involved in matrix deposition in vivo in this model. Administration of the proteoglycan decorin suppressed TGF-beta-induced matrix deposition in the nephritic glomeruli, thus confirming a physiological role for decorin as a regulator of TGF-beta. Inhibitors of TGF-beta may be important future drugs in treating fibrotic diseases caused by overproduction of TGF-beta.

Animals↗

PubMed1990

Persistent effect of TGF-beta 1 on extracellular matrix gene expression in human dermal fibroblasts.

TGF-beta, a potent inducer of the extracellular matrix, is also known to stimulate its own synthesis. In this report we have analyzed long term effects of TGF-beta 1 on its own expression and on the expression of extracellular matrix genes. We demonstrated that 24 hours of incubation of human dermal fibroblasts with TGF-beta 1 (1 ng/ml) under serum free conditions resulted in an elevated expression of TGF-beta 1, collagen alpha 2(I) and fibronectin mRNAs that persisted at least 96 hours after removal of TGF-beta 1. These data suggest the possibility of persistent in vivo activation of target cells following exposure to TGF-beta 1.

Cells, Cultured↗

PubMed2002

The incorporation of fibrinogen into extracellular matrix is dependent on active assembly of a fibronectin matrix.

Fibrinogen is a soluble protein produced by hepatocytes and secreted into plasma, where it functions in hemostasis. During inflammation, the hepatic synthesis of fibrinogen is induced 2-10 fold. Recent studies demonstrate that after an inflammatory stimulus, fibrinogen gene expression and protein production is upregulated in lung epithelial cells, where it is secreted basolaterally and consequently deposited into the extracellular matrix in fibrils that extensively colocalize with fibronectin fibrils. In this study, we show that the deposition of fibrinogen into the matrix of fibroblasts occurred rapidly and in a Rho-dependent manner in response to serum or lysophosphatidic acid; RhoA GTPase signaling is also required for fibronectin matrix assembly. Using mouse embryonic fibronectin-null cells, we show that incorporation of exogenous fibrinogen into matrix fibrils occurred only in the presence of exogenous fibronectin, which is also assembled into matrix fibrils. Furthermore, treatment of fibroblasts and fibronectin-null cells with an antibody that inhibits fibronectin matrix assembly impaired incorporation of fibrinogen into matrix fibrils. Collectively, these data suggest that incorporation of fibrinogen into the extracellular matrix requires active fibronectin polymer elongation into matrix fibrils. From these data, we hypothesize that fibrinogen deposition rapidly changes the topology of the extracellular matrix to provide a surface for cell migration and matrix remodeling during tissue repair.

ADP Ribose Transferases↗

PubMed1991

[Immunohistochemical study on the extracellular matrix components in various renal diseases].

In order to clarify considerable alterations of the extracellular matrix components in various renal diseases, monoclonal antibodies against type IV collagen (IV col), 200-KD laminin (200-KD Lam), 400-KD laminin (400-KD Lam) and heparan sulfate proteoglycan (HSPG) were applied to 142 renal biopsy specimens for the indirect immunofluorescence. These subjects included 5 cases with 1 hour specimen in the transplanted kidney, 32 minimal change nephrotic syndrome (MCNS), 30 mesangial proliferative glomerulonephritis (PGN), 2 focal segmental glomerulosclerosis (FGS), 21 membranous nephropathy (MN), 9 membranoproliferative glomerulonephritis (MPGN), 2 poststreptococcal acute glomerulonephritis (PSAGN), 13 diabetic nephropathy (DN), 16 lupus nephritis (LN), 9 diffuse sclerosing glomerulonephritis (DSGN), 2 amyloid kidney and 1 granulomatous nephropathy in sarcoidosis. In the transplanted kidney, the staining intensity of IV col was stronger than that of 200-KD Lam, 400-KD Lam and HSPG in general. IV col was predominantly distributed throughout the mesangium area and less along the glomerular basement membrane (GBM). The positive stainings with 200-KD Lam along the GBM and that with 400-KD Lam in the mesangium area were weakly recognized. HSPG was mainly detected along the GBM in the linear fashion. In MCNS, the distribution of the extracellular matrix components was mostly identical to that in the transplanted kidney. In the group of the glomerulonephritis showed the proliferations of mesangial cells, such as PGN and MPGN, the staining intensity of both IV col and 400-KD Lam, particularly in the latter, was remarkably increased in the sclerotic lesions. In MN, the thickened GBM was strongly stained with both IV col and 200-KD Lam, and the stainings of 200-KD Lam were more intensive. And still more, by the double labelling method performed for the couple of IV col and immunoglobulins, the correlation between glomerular capillary walls and/or mesangial areas and immunoglobulins deposits became more clear. These findings suggest as follows: (1) both IV col and 400-KD Lam, in particular 400-KD Lam, are possibly involved in the process of glomerulosclerosis: (2) both IV col and 200-KD Lam, in particular 200-KD Lam, are greatly involved in the process of new basement membrane-like materials formation in MN.

Collagen↗

PubMed1988

Extracellular matrix synthesis is required for the movement of sclerotome and neural crest cells on collagen.

During early embryogenesis cells of several different populations disperse by active cell movement from one location to another. Preexisting extracellular materials are major determinants of these dispersal patterns, but the cells are also able to modify their substrata by synthesizing and secreting extracellular matrix molecules as they move. In order to determine the contribution made by these deposited materials, several tissues from the early chick embryo have been cultured in the presence of inhibitors of extracellular matrix synthesis and secretion. The tissues examined were sclerotome cells from differentiated somites and neural crest cells. For comparison, undifferentiated somites were also cultured. The movement of these cells was compared in type I collagen gel culture and in conventional culture on artificial substrata. Inhibitors of collagen synthesis were used (cis-hydroxy proline and L-azetidine-2-carboxylic acid) in addition to a proteoglycan inhibitor (p-nitrophenyl-xylopyranoside) and a secretion inhibitor (monensin). Results indicate that sclerotome cells require collagen synthesis for movement in a collagen matrix. Reversal of the effects of collagen inhibitors, by proline and type II collagen, suggest that sclerotome cells normally condition the type I matrix in order to move in it. Inhibition of proteoglycan synthesis produced the greatest effect on the movement of neural crest cells regardless of the substratum, confirming an important role for these molecules in the crest migratory routes. The attachment of all cells to collagen was highly sensitive to the presence of monensin, which is known to reduce the deposition of glycosaminoglycans and fibronectin. These results suggest that conditioning of the extracellular matrix by newly synthesized material is required for cell attachment and movement during early development.

Animals↗